Failure Patterns of Luminal B Breast Cancer Following Postoperative Adjuvant Radiation Therapy

Abstract

The establishment of surrogate definitions for breast cancer molecular subtypes according to IHC has clinically demonstrated prognostic relevance for improved objective risk profiling and individualization of treatment regimens. Defining and stratifying luminal B subtypes, however, still remains indefinite and is in need of more distinct differentiation due to its heterogeneous clinical and molecular characteristics. This study aims to identify prognostic factors for early relapse in luminal B HER2-negative (LBHER2-) and -positive (LBHER2+) subgroups, and to evaluate failure patterns between the latter and HER2-enriched breast cancer after adjuvant PORT. Medical records of 516 women diagnosed with luminal B or HER2-enriched breast cancer that underwent surgical resection and PORT at Seoul National University Bundang Hospital (SNUBH) from 2003 to 2012 were retrospectively reviewed. Based on available IHC and FISH results, molecular subtypes were defined according to the 2013 St. Gallen International Expert Consensus recommendation as LBHER2- in 258 patients (50.5%), LBHER2+ in 136 patients (26.4%), and HER2-enriched in 122 patients (23.6%). Significant differences were observed between the luminal B subgroups, with LBHER2- demonstrating higher proportions of patients with age younger than 50 years (p=0.012), high histologic grade (p < 0.001), and positive expression of p53 (p=0.007). Patterns of care were also significantly different, with higher rates of systemic therapy omission in LBHER2- patients (p=0.001). After a median follow-up duration of 6.3 years, 10-year OS rates were 87.9% and 97.0% for LBHER2- and LBHER2+, respectively (p=0.062). On multivariable Cox regression analysis, N stage in LBHER2- and N stage and histologic grade in LBHER2+ were identified as independent prognostic factors for relapse within 5 years. When compared with HER2-enriched breast cancer, LBHER2+ expressed lower rates of local recurrence (p=0.046) and brain metastasis (p=0.026). Luminal B breast cancer manifest various patterns of failure among which trends to poorer prognosis is seen in the LBHER2- subgroup. The majority of LBHER2+ patients undergo some form of systemic treatment and demonstrate relatively better clinical outcomes than LBHER2- patients. Further stratification of risk prediction, particularly in the LBHER2- subgroup, and more aggressive systemic treatment are needed to improve treatment outcomes, of which p53 may be a potential marker.